Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Abstract

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH. Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal. Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50-67). WFNS scale was 2 (1-4) and the modified Fisher scale was 3 (1-3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (r_S = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (R _p = -0.42; p < 0.001). Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.

Keywords: autonomic nervous system; baroreflex; cerebral autoregulation; cerebral vasospasm; cerebrovascular regulation; subarachnoid hemorrhage.

Figure 1

Flow diagram of the study. ABP, arterial blood pressure; CBFV, cerebral blood flow velocity; CV, cerebral vasospasm; aSAH, aneurysmal subarachnoid hemorrhage.

Figure 2

An example of the monitoring of (A) 45-year old man without cerebral vasospasm (CV) 12 days after aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured aneurysm in the posterior cerebral artery (PCA). The high values of Mxa [worse cerebral autoregulation (CA), red panel] are counterbalanced with efficient, high-cardiac baroreflex sensitivity (BRS); (B) 67-year old woman during CV 8 days after aSAH from a ruptured aneurysm in the anterior communicating artery (ACom). The high values of Mxa (worse CA, red panel) occur in parallel with disrupted, low BRS; ABP, arterial blood pressure; CBFV, cerebral blood flow velocity; BRS, baroreflex sensitivity; Mxa, mean velocity index; the Mxa above 0.3 is interpreted as pathological.

Figure 3

Spearman correlation of cerebral autoregulation (Mxa) and baroreflex sensitivity (BRS) in patients (A), without cerebral vasospasm (CV), (B) before CV, (C) during CV. A solid red line is a linear regression and dashed lines represent 95% CI.

Figure 4

Time trends (solid red line) and the 95% CI (dashed line) of (A,B) cerebral blood flow velocity (CBFV) and (C,D) baroreflex sensitivity (BRS) in patients (A,C) with and (B,D) without cerebral vasospasm (CV) analyzed in the days that follow aneurysmal subarachnoid hemorrhage (aSAH). The relationship between days and physiological parameters was calculated using multiple linear regression analyses with subjects treated as categorical factors using dummy variables (with respect to the intersubject variability) and a partial coefficient (R_p) between analyzed variables.